Adenosine has been known to have significant effects on mammalian central nervous system. This adenosine effect, at least in part seems to be mediated by its effect on the synaptic transmission. We have recently discovered that adenosine selectively attenuates excitatory synaptic transmission and had no significant effect on inhibitory transmission which seems to be consistent with its generalized depressant effect. Furthermore, adenosine seems to play a critical role in pathophysiology of ischemia and epilepsy. In light of the growing concept of excitotoxicity in these two pathological processed adenosine seems to be an attractive agent counteracting these two neurological insults. The overall objective of this proposal is to determine the mechanism by which adenosine modulates excitatory synaptic transmission and to demonstrate the possible adenosine effect linked to A2 type adenosine receptor. The long term objective is to provide some information on adenosine's role in the physiology of normal neural processes and the pathophysiology of common neurological disorders. Primary dissociated rat hippocampal cultures will be used in conjunction with standard whole-cell, patch-clamp recording techniques. The specific aims of this proposal are: 1) to study and compare the effect of adenosine on identified excitatory and inhibitory neurons by characterizing the adenosine current and its effect on calcium conductance, 2. to compare the pharmacology of GABA/beta and adenosine effects, 3. to study the effect of endogenous adenosine in cultured hippocampal cells.